Multiple sclerosis (MS) is a chronic, frequently progressive, inflammatory central nervous system (CNS) disease characterized pathologically by primary demyelination, usually without initial axonal injury. The etiology and pathogenesis of MS are unknown. Several immunological features of MS, and its moderate association with certain major histocompatibility complex alleles, has prompted the speculation that MS is an immune-mediated disease (Hafler, D. A. and Weiner, H. L., Immunol. Today, 10:104-107 (1989); Compston, D. A. S., "Genetic susceptibility to multiple sclerosis," In: McAlpine's Mutiple Sclerosis (Matthews, B. ed), pp 301-319, London: Churchil Livingstone (1991); Olsson, T., Curr. Opin. Neurol. Neurosurg,, 5:195-202 (1992)).
An autoimmune hypothesis is supported by the experimental autoimmune (allergic) encephalomyelitis (EAE) model, where injection of certain myelin components into genetically susceptible animals leads to T cell-mediated CNS demyelination (Kabat, E. A. et al., J. Exp. Med., 85:117-129 (1947); Lublin, F. D., Spinger Semin. Immunopathol., 8:197-208 (1985)). However, specific autoantigens and pathogenic myelin-reactive T cells have not been definitively identified in the CNS of MS patients, nor is MS associated with other autoimmune diseases. An alternative hypothesis, based upon epidemiological data (Martyn, C., "The epidemiology of multiple sclerosis. In: McAlpine's Multiple Sclerosis, (Matthews, B. ed), pp 3-40, London: Churchil Livingstone (1991) is that an environmental factor, perhaps an unidentified virus, precipitates an inflammatory response in the CNS, which leads to either direct or indirect ("bystander") myelin destruction, potentially with an induced autoimmune component (Lampert, P. W., Am. J. Path. 91:176-208 (1978)). This hypothesis is supported by evidence that several naturally occurring viral infections, both in humans (Rice, G. P. A., Curr. Opin. Neurol. Neurosurg., 5:188-194 (1992)) and animals (Dal Canto, M. C. and Rabinowitz, S. G., Ann. Neurol., 11:109-127 (1982)), can cause demyelination. One commonly utilized experimental viral model is induced by Theiler's murine encephalomyelitis virus (TMEV) (Dal Canto, M. C., and Lipton, H. L., Am. J. Path., 88:497-500 (1977)).
The limited efficacy of current therapies for MS and other demyelinating diseases (Goodkin, D. E. et al., Clev. Clin. J. Med., 59:63-74 (1992)), has stimulated interest in novel therapies to ameliorate these diseases (Martin, R., et al., Ann. Rev. Immunol., 10:153-187 (1992); Steinman, L., Adv. Immunol., 49:357-379 (1992); Weiner, H. L., et al., science 259:1321-1324 (1993)). However, due to the apparently complex etiopathogenesis of these diseases, potentially involving both environmental and autoimmune factors, the need still exists for an effective treatment of these demyelinating disorders.